Genetic polymorphisms linked to poor melanoma outcomes

April 3, 2007

Washington - Certain variants in the interleukin 10 (IL-10) promoter region can predict poor outcomes in patients with malignant melanoma, including tumor ulceration and recurrence, suggests research presented at the recent 60th annual meeting of the Society of Surgical Oncology, here.

Washington - Certain variants in the interleukin 10 (IL-10) promoter region can predict poor outcomes in patients with malignant melanoma, including tumor ulceration and recurrence, suggests research presented at the recent 60th annual meeting of the Society of Surgical Oncology, here.

The research, conducted at the University of Texas M.D. Anderson Cancer Center, is based on a genomic study of 146 patients with melanoma of all stages, according to Web-based news source docguide.com.

The study’s main finding was that a particular haplotype called ATA is associated with substantial increases in rates of ulceration and recurrence after treatment.

The researchers previously identified three locations in the IL-10 promoter sequence as candidate prognostic markers. IL-10 has both immunoregulatory and angiogenic activity, and previous studies have linked variants in the IL-10 promoter to cancer susceptibility and prognosis.

More recent analysis showed that variants in two of the three genes were closely coupled, so that there were just three possible gene combinations worthy of study: ATA, ACC and GCC.

The new study found that ATA, seen in 60 participant patients (41 percent of the total), was a powerful predictor of tumor ulceration. Three-quarters of those with two copies of the ATA haplotype developed ulceration, compared with no patients with two copies of the ACC combination. Among the 114 patients in the trial whose tumor-ulceration status was recorded, 23 percent developed ulceration.

Similarly, multivariate analysis identified ATA homozygosity as effectively predicting post-treatment disease recurrence - making it a substantially better predictor than such standard factors as tumor thickness, disease stage and sentinel lymph-node involvement.

“Identification of clinically relevant polymorphisms may allow more accurate selection of high-risk patients,” the study’s authors conclude, adding that the results suggest IL-10 may also provide targets for new melanoma therapies.